The overall objectives of the Arizona SCOR are to determine the pathogenesis, natural histories, methods of early detection, and possible means of prevention of airways obstructive diseases (AOD). Nine closely related epidemiological, physiological, and experimental projects, supported by four cores provide a coordinated multidisciplinary interdepartmental program. The data from our longitudinal study of a general population sample including >1700 households and >4500 subjects will continue to be analyzed to identify innate and extrinsic risk factors for the development and progression of AOD. Data will continue to be collected on selected subsets of this population to maximize follow-up, to answer specific hypotheses, or to carry out detailed studies of lung structure and function. The cohort of >1200 newborns and their families enrolled several years ago will continue to be followed to determine the importance of inherited characteristics and events in infancy (especially viral lower respiratory tract illnesses) in determining lung function, bronchial reactivity, and immunologic status later in life. Detailed studies of lung growth and respiratory physiology of infants and children will be continued. The effects of smoke exposure on the developing lung will be assessed in infants and in an animal model. An already enrolled population of middle aged working subjects and families with bronchial hyperresponsiveness (BHR) will continue to be studied, with an emphasis on relating BHR and other host factors to the development and progression of airways abnormalities. Our canine model of viral bronchiolitis will be expanded to determine how induced "allergy" influences the effects of the viral infection, especially in regard to BR and immunologic status. The basic mechanisms involved in BR will be studied in vivo in a rabbit model with many features of allergic asthma and in excised airway preparations. Since preliminary work suggests an important role of the parasympathetic system in regulating BR, a detailed study of muscarinic and NANC receptors in the lung is included as well as a project to study the electrophysiology of parasympathetic airway ganglia which may be important in modulating airway function.